The Ketogenic Diet and Its Effect on Bone Mineral Density: A Retrospective Observational Cohort Study
03 April 2019
30 May 2019
09 August 2019 (online)
Background During long-term follow-up of children treated with the ketogenic diet therapy (KDT) have an increased incidence of bone fractures. However, the exact contribution of KDT to a decreased bone mineral density (BMD) remains unclear.
Objective This study aimed to evaluate (changes in) BMD in children treated with KDT and to evaluate whether intravenous bisphosphonate therapy may be effective.
Design In this retrospective, observational cohort study, all children treated with KDT from 2010 until 2018 at the Radboudumc Amalia Children's hospital were included. Patients who were on KDT for more than 6 months and who had at least two dual-energy X-ray (DXA)-scans were eligible for inclusion for longitudinal analysis. Z-scores of DXA-scans were compared over the course of time.
Results In 34 out of 68 patients, one or more lumbar DXA-scans were performed, with a mean lumbar Z-score of −1.32 ± 1.74. Of these 68 patients, 8.8% got a fracture during KDT, and also 8.8% got kidney stones. In 20 patients, more than one DXA-scan was performed. A statistically not significant decrease in BMD (0.22 Z-score/year) was found. However, there was an increase in BMD in the five patients treated with intravenous bisphosphonate therapy. This was statistically significant in comparison to the nonbisphosphonate treated group (p = 0.034).
Conclusion Children on KDT have low normal BMD which may decrease further during KDT. For this reason monitoring of BMD is crucial, as is monitoring of kidney stones and hypercalciuria. Intravenous bisphosphonate therapy may have a positive effect, when other therapies have failed.
- 1 Keene DL. A systematic review of the use of the ketogenic diet in childhood epilepsy. Pediatr Neurol 2006; 35 (01) 1-5
- 2 Wheless JW. History of the ketogenic diet. Epilepsia 2008; 49 (Suppl. 08) 3-5
- 3 Kossoff EH, Zupec-Kania BA, Auvin S. , et al; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 2018; 3 (02) 175-192
- 4 Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 2007; 48 (01) 43-58
- 5 Neal EG, Chaffe H, Schwartz RH. , et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008; 7 (06) 500-506
- 6 Klepper J, Leiendecker B. GLUT1 deficiency syndrome--2007 update. Dev Med Child Neurol 2007; 49 (09) 707-716
- 7 Wexler ID, Hemalatha SG, McConnell J. , et al. Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 1997; 49 (06) 1655-1661
- 8 Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol 2006; 48 (12) 978-981
- 9 Kang HC, Chung DE, Kim DW, Kim HD. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004; 45 (09) 1116-1123
- 10 Bergqvist AG, Schall JI, Stallings VA. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia 2007; 48 (01) 66-71
- 11 Bergqvist AG, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 2008; 88 (06) 1678-1684
- 12 Simm PJ, Bicknell-Royle J, Lawrie J. , et al. The effect of the ketogenic diet on the developing skeleton. Epilepsy Res 2017; 136: 62-66
- 13 Furth SL, Casey JC, Pyzik PL. , et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol 2000; 15 (1,2): 125-128
- 14 Sampath A, Kossoff EH, Furth SL, Pyzik PL, Vining EP. Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol 2007; 22 (04) 375-378
- 15 Saraff V, Högler W. Endocrinology and adolescence: osteoporosis in children: diagnosis and management. Eur J Endocrinol 2015; 173 (06) R185-R197
- 16 Messina C, Lastella G, Sorce S. , et al. Pediatric dual-energy X-ray absorptiometry in clinical practice: what the clinicians need to know. Eur J Radiol 2018; 105: 153-161
- 17 Kossoff EH, Pyzik PL, Furth SL, Hladky HD, Freeman JM, Vining EP. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002; 43 (10) 1168-1171
- 18 Matos V, van Melle G, Boulat O, Markert M, Bachmann C, Guignard JP. Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J Pediatr 1997; 131 (02) 252-257
- 19 Van der Louw EJTM, Van den Hurk TAM, Catsman-Berrevoets CE. Guideline for professionals of the ketogenic diet treatment for children with intractable epilepsy and metabolic diseases 2015. Available (in Dutch) at: https://www.dietistenvoorspierziekten.nl/upload/docs/zorgpad-ketogeen-dieet-behandeling-bij-kinderen-versie-mei-2015_0.pdf . Accessed June 17, 2019
- 20 Gordon CM, Leonard MB, Zemel BS. ; International Society for Clinical Densitometry. 2013 Pediatric Position Development Conference: executive summary and reflections. J Clin Densitom 2014; 17 (02) 219-224
- 21 McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics 2009; 124 (02) e300-e304
- 22 Ward LM, Konji VN, Ma J. The management of osteoporosis in children. Osteoporos Int 2016; 27 (07) 2147-2179
- 23 Nasomyont N, Hornung LN, Gordon CM, Wasserman H. Outcomes following intravenous bisphosphonate infusion in pediatric patients: a 7-year retrospective chart review. Bone 2019; 121: 60-67